He was studying loneliness and isolation. She was studying love and desire. When they found themselves together, they gravitated toward her end of the continuum of social connection.

John Cacioppo was living in Chicago and Stephanie Ortigue in Geneva when they met—in Shanghai. ... On the last night of the conference, they happened to be seated next to one another at an official dinner, and soon became absorbed in conversation. “She was wonderful and brilliant and funny and I was completely taken by her,” Cacioppo says.

They both felt the chemistry but had to return to their respective homes the next day. Before parting ways they walked out of the restaurant together and noticed a beautiful moon hanging over the city. He snapped a picture of it. “A couple weeks later, she e-mailed me and asked if I could send her the picture,” Cacioppo says—a request his wife now confesses was just an excuse to strike up another conversation.

Within weeks they arranged to meet again, and from there their love unfurled. ... Within eight months they were engaged, and a season later they had married.

Their romantic story and collaborative work has been covered by a number of professional and popular media outlets, including the press office at the University of Chicago. The newsroom issued a press release on February 13, 2014 to coincide with Valentine's Day:

A region deep inside the brain controls how quickly people make decisions about love, according to new research at the University of Chicago.

The finding, made in an examination of a 48-year-old man who suffered a stroke, provides the first causal clinical evidence that an area of the brain called the anterior insula “plays an instrumental role in love,” said UChicago neuroscientist Stephanie Cacioppo, lead author of the study.

The study (Cacioppo et al., 2013) showed no such thing (in my opinion), and I'll return that in a moment. But for now I'll point out the Cacioppo spin didn't translate so well to other reports about this neurological patient. According to the Fox News affiliate in Little Rock, AK:

Love at first sight does not exist, claim researchers in the Current Trends in Neurology journal.

A stroke patient had a damaged anterior insula -- which is the part of the brain which controls how quickly we fall for someone.

They found that he could make decisions about lust normally but needed longer to think about love.

The researchers say this finding "makes it possible to disentangle love from other biological drives".

The Chicago researchers never said that love at first sight is a myth. But that didn't stop the British tabloid Metro from running that headline, while the Times of India declared:

A new study suggests that love at first sight is a myth and it does not exist.

According to the study, the speed at which we fall for someone is controlled by a region in the brain called the anterior insula, Metro.co.uk reported.

All this curt tabloid fodder contradicts the meet-cute trope of the Cacciopo's own relationship. But their study itself is also quite problematic. It doesn't support the authors' contention, in my view, and here's why.

WITH Apple widely expected to release its iPhone 5 on Tuesday, Apple addicts across the world are getting ready for their latest fix.

But should we really characterize the intense consumer devotion to the iPhone as an addiction? A recent experiment that I carried out using neuroimaging technology suggests that drug-related terms like “addiction” and “fix” aren’t as scientifically accurate as a word we use to describe our most cherished personal relationships. That word is “love.”
. . .

...most striking of all was the flurry of activation in the insular cortex of the brain, which is associated with feelings of love and compassion. The subjects’ brains responded to the sound of their phones as they would respond to the presence or proximity of a girlfriend, boyfriend or family member.

In Tal Yarkoni’s recent paper in Nature Methods [PDF], we found that the anterior insula was one of the most highly activated part of the brain, showing activation in nearly 1/3 of all imaging studies!

Here's where the Cacciopos and their anterior insulae come in...

The Common Neural Bases Between Sexual Desire and Love

That was the title of a review article that conducted a statistical meta-analysis of the neuroimaging literature on "love" compared to "lust" (Cacioppo et al., 2012). The emphasis was on the similarity of brain regions activated by purported experimental elicitors of these complex behavioral and cognitive states (e.g., "look at a picture of your spouse" vs. close friend, or "watch porn" vs. non-porn). However, they did report a "gradient" of differential activation from the anterior "love" insula to the posterior "lust" insula, as shown below.

In their more recent paper, Cacioppo et al. (2013) wanted to move beyond correlational data by testing a neurological patient with damage in the anterior insula. This is generally a good strategy to evaluate whether your highly vaunted theory based on fMRI data can hold up to causal manipulations, or in this case an accident of nature. If a person with anterior insula damage cannot feel love, then you'd say that region is necessary for feelings of love. If their ability to love is unaffected, then you'd say the anterior insula is not very important.

We can go even further and ask if that patient with damage to anterior insula – but sparing of posterior insula – can still feel lust but not love. In that case, you'd say there's a dissociation between love and lust in the anterior vs. posterior insula. 2

But that's not what the study was about!! Instead, it was about a speeded response task: look at pictures and quickly decide whether the person evokes feelings of love (or desire, in separate blocks). From the outset, I'll say that reaction times (RTs) in this task really have nothing to do with love, even as it was conceived in the fMRI experiments (i.e., "look at a picture of your spouse" and even "look at a picture of your child" - !!)

The participant in the study was a 48 year old heterosexual man who had a stroke affecting a fairly large portion of the right insula [I think], which is good for the investigators because "lust" seems to "localize" to the left posterior insula in their schematic above. We don't know a whole lot about this man (like, how long ago was his stroke?), other than that "At the moment of evaluation, the patient showed no symptoms and his neurological exam was normal." We'll just have to trust them on that...

Oh, and he was cognitively normal on some brief screening tests, not depressed or anxious, and fine in two social cognition tasks (including empathy for pain, a task where other persons with anterior insular lesions show deficits).

On to the task. The patient and 7 age- and sex-matched controls viewed 40 pictures in blocks of 20. In two of the blocks, the participants decided whether the sexily dressed girl/young woman (aged 18-30) in the photo was "relevant to sexual desire" (yes/no) or "relevant to love" (yes/no). Each image was viewed twice. Only the RTs on "yes" responses were evaluated, for some unknown reason, so we don't know if the patient was faster/slower than controls to reject a photo.

The patient behaved similarly to controls in the "lust" task. It took him just under a second, 926 milliseconds (ms), to respond "yes" when he desired the sexy young girl in the picture, compared to 959 ms for controls [remember, these guys are 48 and the girls are as young as 18], which did not differ. The patient said "yes" to lust 58% of the time vs. 61% for controls. The authors write (PDF):

The anamnesis indicated that the patient was unaware of any differences in his feelings of love or desire, whereas behavior testing revealed a selective deficit for love (but not sexual desire).

In the "love" task, the patient said "yes" to love 35% of the time vs. 43% for controls (which again did not differ). For RT, the patient took 1279 ms to say "yes" to love vs. 1020 ms for controls. And this constitutes his selective deficit for love!! It took him 259 ms longer to decide that a stranger in a photo in a laboratory task was "relevant to love." And we don't know how long it took him to say "no." And he reported no subjective change in his feelings of love, and no significant others or family or friends were queried about this.

The patient could have been slower to make that decision for any number of reasons that have nothing to do with “playing an instrumental role in love.” I won't belabor the point, but this particular region of the brain is implicated in many different functions.

With all due respect to the authors, I don't understand how this paper was published in its current form.3

Sunday, February 09, 2014

Can neuroscience illuminate the nature of human relationships? Or does it primarily serve as a prop to sell self-help books? The neurorelationship cottage industry touts the importance of brain research for understanding romance and commitment. But any knowledge of the brain is completely unnecessary for issuing take-home messages like tips on maintaining a successful marriage.

In an analogous fashion, we can ask whether successful psychotherapy depends on having detailed knowledge of the mechanisms of “neuroplasticity” (a vague and clichéd term). Obviously not (or else everyone's been doing it wrong). Of course the brain changes after 12 sessions of psychotherapy, just as it changes after watching 12 episodes of Dexter. The important question is whether knowing the pattern of neural changes (via fMRI) can inform how treatment is administered. Or whether pre-treatment neuroimaging can predict which therapy will be the most effective.

However, neuroimaging studies of psychotherapy that have absolutely no control conditions are of limited usefulness. We don't know what sort of changes would have happened over an equivalent amount of time with no intervention. More importantly, we don't know whether the specific therapy under consideration is better than another form of psychotherapy, or better than going bowling once a week.

In “The Devil’s Dictionary,” Ambrose Bierce defined love as “a temporary insanity curable by marriage.” Enter Sue Johnson, a clinical psychologist and couples therapist who says that relationships are a basic human need and that “a stable, loving relationship is the absolute cornerstone of human happiness and general well-being.” To repair ailing partnerships, she has developed a new approach in marriage counseling called Emotionally Focused Therapy, or EFT, which she introduces in her new book, “Love Sense.”
...

Johnson believes EFT can help couples break out of patterns, “interrupting and dismantling these destructive sequences and then actively constructing a more emotionally open and receptive way of interacting.” She aims to transform relationships “using the megawatt power of the wired-in longing for contact and care that defines our species,” and offers various exercises to restore trust.

Most interesting to me was Johnson’s brain-scanning study. Before EFT therapy, unhappily married women participating in the study reported considerable pain from an electric shock to the ankle as they held their husbands’ hands. After 20 sessions of EFT, however, these now more securely attached women judged their pain as only “uncomfortable” and their brain scans showed no alarm response. Secure attachment appears to change brain function and reduce pain.

Initial questions:

Is there a “wired-in longing for contact and care that defines our species”? {my needy cat seems to long for contact and care}

But Johnson too often focuses on attachment to the exclusion of other “megawatt” brain systems. Remarkably, she lumps romantic love with attachment, saying “adult romantic love is an attachment bond, just like the one between mother and child.” In reality, romantic love is associated with a constellation of thoughts and motivations that are strikingly different from those of attachment. My research bears out that humankind evolved distinct but interrelated brain systems for mating and reproduction: the sex drive (to seek a range of partners); feelings of romantic love (to focus one’s mating energy on a single partner); and feelings of attachment (to drive our forebears to form a pair-bond to rear their young together). Each brain system is associated with different neurochemicals; each is a powerful drive that still plays a continuing role in partnership stability.

More questions:

Are there distinct (but interrelated) brain systems for the sex drive, romantic love, and feelings of attachment? {I actually find this to be plausible}

Is each brain system associated with different neurochemicals? {i.e. testosterone, dopamine, and oxytocin, respectively. I find this to be less plausible, or at least a bit simplistic.}

It's time to correct the misperceptions and overinterpretations that have arisen from this research!!

Since there are a number of issues to tackle here – too many for a single post – I'll concentrate on only one of them here.

I Wanna Hold Your Hand

In 2006, Dr. James Coan and colleagues published a neuroimaging paper suggesting that the brains of happily married women showed an attenuation of activity related to emotion and threat when they held the hands of their husbands (Coan et al., 2006). Threat was induced experimentally by presenting a stimulus which occasionally signaled that a mild electric shock would be delivered to the ankle (20% of the time). Holding the hand of a male stranger also attenuated the hemodynamic response in some of these regions, relative to a no hand-holding control condition.2

Backing up a bit, the participants in the study were 16 heterosexual couples who rated their marital satisfaction as at least 40 on the Satisfaction subscale of the 50 point Dyadic Adjustment Scale (DAS). Total scores on the DAS were 126 for husbands (on a 151 point scale) and 127 for wives.3

The experimental design is illustrated below. The red X indicated a 20% chance of shock.

Figure adapted from a 2011 presentation by Coan (PDF), part of which can be viewed here.

At the end of each block, the women rated their subjective levels of unpleasantness and arousal on a 5 point scale. The results of the hand-holding manipulation were a bit weak. Unpleasantness ratings in the husband-hand condition were indeed significantly lower than no-hand (p=.001), but only marginally so compared to the stranger-hand condition (p=.05, with p<.05 being the usual cutoff for significance). The arousal ratings for husband-hand vs. no-hand (p=.07) and stranger-hand vs. no-hand (p=.08) were not officially significant either.

This raises a question I considered in 2006: why were the wives the only ones who were scanned?

...what about married women holding their mothers' hands? married men holding their wives' hands? unmarried women holding their partners' hands? single women holding the hands of their best friends? Perhaps the authors started with the relationship that they most expected to yield significant results...

The subjective effects of spousal-handholding were not enormous in women, which might explain why we've never seen data from husbands (i.e., perhaps there were no effects on self-report and/or neural activity). The highly-touted correlations between the wife's relationship quality rating and attenuation of threat-related brain signals weren't especially impressive either: −.59, p = .02 for the left superior frontal gyrus, −.47, p = .07 (not significant) for the right anterior insula, and −.46, p = .08(not significant) for the hypothalamus. These numbers represent the magnitude of reduction in threat-related activity when holding the husband's hand, and were interpreted to suggest that the attenuations in pain (insula) and stress (hypothalamus) were related to the strength of attachment.4

Emotionally Focused Therapy

This finally brings us to the recent paper by Johnson et al. (2013). They followed the imaging protocol of Coan et al. in a set of 35 married couples who were screened for relationship dissatisfaction and scanned both before and after 23 sessions of EFT couples counseling (range of 13 to 35 sessions over 3.25 to 8.75 months). On average, the couples were white Canadians 44-45 years of age, married for 17 years. In contrast to the happy couples described above (DAS scores of 127), these couples reported moderate levels of relationship distress, with DAS scores of 80-97. For various understandable reasons, only 23 couples completed pre- and post-EFT fMRI scans. Again, only the wives were scanned.

Still, retaining 23 couples over 6 months of treatment is no mean feat. However, I will again note that there is no control condition in this experiment, so we can't know whether any changes are specifically due to the treatment of interest.

Session and therapy length varied depending on the couples' presenting concerns and their progression through EFT-defined therapeutic change events [18], [28]. Specifically, when a couple was deemed according to EFT guidelines to have achieved 1) “softening” – a state of vulnerability and sharing of attachment related needs between the partners [37] – and 2) “consolidation” – where the therapist works with the couple to review treatment gains – treatment was terminated.

I am not qualified to comment on EFT and will not discuss it further, beyond saying that post-therapy DAS scores were significantly increased (pre-EFT mean=81 and post-EFT mean=96) but still, on average, in the moderately distressed range. Unpleasantness and arousal ratings in the husband-hand fMRI condition were lower after EFT.

The fMRI results after EFT were.... complicated, as shown below, and involve what appears to be post-hoc reasoning in relation to initial marital strife. Percent signal change was assessed for all voxels in the ROIs that were reported by Coan et al., which is a good and unbiased method for analyzing an independent dataset.

Fig. 2 (Johnson et al., 2013). Point estimates of percent signal change graphed as a function of EFT (pre vs. post) by handholding (alone, stranger, partner) and DAS score. Point estimates were computed separately for individuals high (+1SD) and low (−1SD) in DAS. Point estimates reflect average percent signal change (threat – safe) from all voxels activated in the original Coan et al. handholding study.

But the results are a little hard to interpret for the wives with high DAS scores, who nonetheless still experienced relationship distress. The intervention had no effect on their global threat-related brain response when holding their husbands' hands. In contrast, those with lower DAS scores showed a post-EFT increase in the threat response in the no-hand condition, a large reduction for stranger-hand, and a very large reduction for husband-hand.

Next the authors moved towards analyzing specific ROIs. I'll skip the husband vs. alone comparisons because these are less relevant. Well, except I'll quote this bizarre finding (which isn't terribly relevant, just hard to explain):

Interestingly, participants with higher DAS scores were generally less active in the substantia nigra/red nucleus when holding hands with their partners relative to when alone, independent of EFT, F(1,49.5)=6.6, p=.01.

OK then. What about the husband vs. stranger comparisons? There were a number of brain areas that showed pre- to post-therapy decreases that did not differ for husband-hand vs. stranger-hand.5 These regions included the right insula, which was related to relationship quality in the Coan et al. (2006) study. The two regions with positive findings (i.e., threat-related reductions in husband-hand and increases in stranger-hand) are right dorsolateral prefrontal cortex (dlPFC) and left supplementary motor area (SMA). No relationships to DAS score were reported.

What have we learned from this study, and how does it inform the practice of EFT? If we take it at face value, the one consistent finding between the two experiments is that the threat response in right dlPFC was attenuated when holding the husband's hand, relative to holding a stranger's hand. If this neural region serves to downregulate negative emotional responses expressed elsewhere (as described below), there were no downstream regions in need of downregulation:

The dlPFC in particular supports explicit, cognitive, or “reappraisal” based self-control strategies active during unpleasant emotional states [54]. ... The relative post-EFT inactivity of the dlPFC implies further that a secure connection with an attachment figure does not help individuals to maintain equilibrium by boosting self-regulatory capabilities per se but by reducing the perception and significance of threats, thus obviating the need for self-regulation to occur [13].

Having some kind of autonomic measure of threat perception (e.g., skin conductance or heart rate) would be useful in verifying this hypothesis. The authors don't interpret their other major finding, a similar effect in the left SMA (a motor control region).

The final question remains unanswered: how does this study inform the practice of EFT? The authors state:

Ultimately, our handholding paradigm has provided a unique opportunity to test some of the proposed mechanisms of social support in general, and EFT in particular, all at the level of brain function, in vivo.

But not all of their predictions were supported. In particular, to explain the changes in neural threat processing observed in the no-hand condition, they resorted to an alternate model of therapeutic change:

We predicted that EFT would not affect neural threat responding during the alone condition. ... [But] threat-related activity during the alone condition actually increased as a function of EFT in regions such as the dACC and portions of the PFC. Increased reactivity in these regions suggests a possible cost to increasing one's dependence upon social resources: that it becomes more difficult to tolerate being alone.
...

This is not what we observed. Although positivity ratings did not change, subjective arousal actually decreased. This suggests an alternative hypothesis: that EFT either trained or motivated clients to be more effective self-regulators even when alone. ... Although EFT focuses strongly on interpersonal attachments and interdependence, doing so may also increase self-regulatory motivation as clients come to value fostering effective relationships in part through self-regulatory effort.

I'm not sure that I understand this formulation, or that a dissociation between behavioral self-report and dACC activity warrants a reinterpretation of EFT's therapeutic effects. Ultimately, I don't feel like a BS-fighting superhero either, because it's not clear whether Magneto has effectively corrected the misperceptions and overinterpretations that have arisen from this fMRI research.

2 The specific neuroimaging results were a bit less straightforward and easily interpreted than this. Regions of interest (ROIs) were defined by determining which areas were activated by the red X threat compared to the safe signal in the no-hand condition. This threat response was attenuated in the husband-hand vs. no-hand condition in the ventral anterior cingulate cortex (vACC), left caudate, superior colliculus, posterior cingulate, left supramarginal gyrus, and right postcentral gyrus. The threat response was also specifically attenuated in husband-hand vs. stranger-hand only in right dorsolateral prefrontal cortex, considered a “cognitive control” area. Finally, the stranger-hand vs. no-hand comparison revealed attenuation in the same bold blue regions above.

3 However, the correlation between husbands' and wives' DAS scores was not significant. Hmm... Would knowledge of this finding create any discord?

4 I won't get into how those single functions were assigned to these two complex and diverse brain regions.

5Johnson et al. (2013): “In the vmPFC, left NAcc, left pallidum, right insula, right pallidum, and right planum polare, main effects of EFT revealed general decreases from pre- to post- therapy in threat activation, regardless of whose hand was held.”

Tuesday, February 04, 2014

We all start to forget things, have word finding problems, and generally slow down cognitively once we get older, right? Wrong, says a recent paper by Ramscar et al. (2014), The Myth of Cognitive Decline: Non-Linear Dynamics of Lifelong Learning [free PDF].

Well, the real answer is more like, “it’s complicated,” as the first author explained in a blog post on the the paper. A giant in the field of cognitive aging quickly retorted, oh no it's...

...“Clever-Silly” comes irresistibly to mind, but this must be inadvertent fall-out from an elderly brain overstuffed by failure to assimilate the vast literature on cognitive aging.

The Rise of Academic Blogging

In the last post, I noted the potential Decline of Neurocriticism. At the same time, more and more people have started their own neuroscience and psychology blogs (which magnifies the channel factor, as Roger Dooley noted). And it's not only the SciCom crowd, which includes science journalists and aspiring science writers who aim to leave lab work behind. Some professional societies like the Society for Neuroscience are getting into the game (BrainFacts.org Blog in 2012), while some like APS We're Only Human (2010) and the venerable BPS Research Digest (2005) have been around a while longer.

An increasing number of academics are starting to blog as well. The Myth of Cognitive Decline provides a perfect example of the rapid (and serious) exchange of ideas that's possible in a "non-peer reviewed" format. Certainly, heavyweight academic blogs such as Language Log, and Statistical Modeling have existed for 10 years, but I think academic blogging is on the rise, perhaps even more so in psychology than neuroscience.

For over almost five decades, Professor Patrick Rabbitt has been among the most distinguished of British cognitive psychologists. His work has been widely influential in theories of mental speed, cognitive control, and ageing, influencing research in experimental psychology, neuropsychology, and individual differences.

So if someone makes a bold new claim about cognitive aging, they really should listen to what he says.

In his inaugural post, Age and the overstuffed mind, Prof. Rabbitt lightly and humorously skewers Ramscar et al.'s (2014) claim that cognitive decline is a myth (which received extensive coverage in the press). He unfavorably compares their model to the Homer Simpson model, summarized as, “Every time I learn something new it pushes something out”:

The Simpson model makes no prediction for decision speed because it posits finite data capacity beyond which no increment, and so no further slowing, can occur. In this respect it is more elegant than the Ramscar model which makes no allowance for stabilisation or even shrinking of the data store by data attrition (forgetting) or displacement.

However, Rabbitt makes the astute observation that the paper may have been deliberately provocative:

In conclusion: unlike the Simpson model, which was arguably first empirically tested seventy years ago and still offers a touching insight into the human condition, the Ramscar model may be intended only as a provocation and to stimulate discussion. The boundary between provocation and exasperation is narrow, and is shifted by the experiences and intellectual commitments of an audience.

Sunday, February 02, 2014

In the last post, I celebrated Eight Years of Neurocriticism but wistfully noted that this blog's popularity peaked in 2012. The traffic last year showed a decline to 2009-2010 levels. Why did this happen? And does it matter? No it does not, but it gives me the opportunity to comment on the state of a specialized little corner of science blogging. The sort of piece where people say things like “blogging as a chance to exercise our voices doesn’t seem to be going anywhere” and “the blog is dead.”

Except not that.

@practiCalfMRI politely suggested it's the quality of visitor that counts. In 2013 the Average Time on Site for my homepage was indeed up 25%, but I could have been inadvertently cherry picking the data...

Commenters on the post anticipated some of my thoughts. Perhaps it was related to the demise of Google Reader, said one. A drop did occur when the service stopped in July 2013, but traffic started trending downward in April-May 2013. So I don't think this can explain it. Instead, the format may have been a victim of its own success and run its course. As another commenter aptly put it:

What happened? Well, what always happens: with time, people get bored. Of anything. From marriage to cereal bar flavor. When you started Neurocritic, it was new, and people were sick of all the neurocrap published out there. Then, the neurocrap people and others, started realizing that talking crap about neuro stuff got a lot of hits! And so everybody started doing it, from Voodoo correlations to Retraction Watch. It was the fashionable thing to do. That's when it got boring.

As I've said before, this general trend has been useful in pointing out flawed studies, overblown conclusions, and overly hyped press releases. But some working neuroscientists thought the naysaying had gotten a little out of hand, because expert critiques are easily misinterpreted. A little neuronuance is needed here, the middle ground that acknowledges limitations yet avoids global condemnations. Around this time, I initiated my own little backlash against the anti-neuro backlash by starting a new blog, The Neurocomplimenter.

Daniel Engbar went out on a limb and proposed that “the public turned its back on neuro-hype” long ago (in 2008) and that “2008 may also have been the high point for critical neuroscience blogging.” But I place the date later than that, in 2012. Nevertheless, popular new blogs like Neurobollocks started after then, and Neuroskeptic shows no signs of slowing down. And there's plenty of blogging to be done that doesn't involve neurocriticism.

Maybe I'm just getting boring (or bored). So perhaps it's time to use a new platform like Tumblr to post animated gifs of brains from cheesy horror movies —OMG Neurocritic!

Instead of blogging, people are posting to Tumblr, tweeting, pinning things to their board, posting to Reddit, Snapchatting, updating Facebook statuses, Instagramming, and publishing on Medium. ... Blogs are for 40-somethings with kids.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.